Cu-Catalyzed Aminodifluoroalkylation of Alkynes and α-Bromodifluoroacetamides

Article abstract of DOI:10.1021/acs.joc.7b01313

The copper-catalyzed highly regioselective aminodifluoroalkylation of alkynes and α-bromodifluoroacetamides was realized for the first time. With this method, 3,3-difluoro-1H-pyrrol-2(3H)-ones were constructed in a single step from various alkynes and α-b

Full text of DOI:10.1021/acs.joc.7b01313

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Note
Cu-Catalyzed Aminodifluoroalkylation of
Alkynes and #-Bromodifluoroacetamides
Yunhe Lv, Weiya Pu, Qian Chen, Qingqing Wang, Jiejie Niu, and Qian Zhang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b01313 • Publication Date (Web): 10 Jul 2017
Downloaded from http://pubs.acs.org on July 10, 2017
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CuꢀCatalyzed Aminodifluoroalkylation of Alkynes and
αꢀBromodifluoroacetamides
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Yunhe Lv,†* Weiya Pu,† Qian Chen,† Qingqing Wang,† Jiejie Niu† and Qian Zhang‡*
†College of Chemistry and Chemical Engineering, Anyang Normal University, Anyang, 455000, P. R. China
‡Jilin Province Key Laboratory of Organic Functional Molecular Design & Synthesis, Department of Chemistry,
Northeast Normal University, Changchun 130024, China
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The copperꢀcatalyzed highly regioselective aminodifluoroalkylation of alkynes and
αꢀbromodifluoroacetamides is realized for the first time. With this method,
3,3ꢀdifluoroꢀ1Hꢀpyrrolꢀ2(3H)ꢀones could be constructed in a single step from various alkynes
and αꢀbromodifluoroacetamides substrates without using any extra oxidant.
The introduction of fluorine atoms or fluorinated moieties can alter molecular physical and
chemical properties and biological activities in a dramatic way.1 Nitrogenꢀcontaining
heterocycles are key core of bioactive molecules.2 Therefore, the efficient synthesis of
fluorinated nitrogenꢀcontaining heterocycles is highly desirable for exploration of new
pharmaceuticals.3 As part of our ongoing study on aminofluorination reaction of alkenes and
aminoarylation of alkynes using Nꢀfluorobenzenesulfonimide (NFSI) as nitrogen source and
the fluorine or aryl source,4 we try to synthesize fluorinated nitrogenꢀcontaining heterocycles
directly from alkynes by seeking a reagent with both fluorine and nitrogen moieties. Our
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literature survey showed that αꢀbromodifluoroacetamides might be a suitable reagent for this
purpose.5 As we know, the gemꢀdifluoromethylene group (CF2) not only acts as lipophilic
hydrogen bond donors and as bioꢀisosteres of alcohols and thiols, but also may significantly
improve the biological stability.6 Very recently, via reductive cleavage of CꢀBr bond,
αꢀbromodifluoroacetamides was successfully utilized as a fluoroalkyl radical reagent which
can be trapped by a series of unsaturated compounds.5cꢀd On the other hand, in the presence of
transitionꢀmetal, oxidant and base, αꢀbromodifluoroacetamides may also be used as a suitable
reagent for amination via cleavage of NꢀH bond in Nꢀaryl amides.7 Therefore, we reasoned
that in the presence of one suitable catalyst, the above two processes could be consequentially
realized to fulfill a catalytic cycle. Thus the gemꢀdifluoro group and nitrogen atom can be
simultaneously installed into an unsaturated CꢀC bond, which will lead a gemꢀdifluorinated
azaꢀheterocycle (Scheme 1).
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Scheme 1 Aminodifluoromethylation of Alkynes and Our Strategy
In contrast to the recent significant progress in the difluoromethylation of arenes5b,8 and
difluoromethylation difunctionalization of alkenes,5d,9 efficient difluoroalkylation of less
reactive alkynes are less abundant. Recently, examples of metalꢀcatalyzed difluoromethylation
difunctionalization of alkynes, such as halodifluoroalkylation, aryldifluoromethylation,
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cyanodifluoroalkylation, and carbodifluoroalkylation was realized to provide molecules with
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important
difluoroalkyl
units
(C=CCF2R).10
However,
to
our
knowledge,
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aminodifluoroalkylation of simple alkynes has never been reported. Herein we report the first
example of a copperꢀcatalyzed highly regioselective aminodifluoroalkylation of alkynes with
αꢀbromodifluoroacetamides as both fluorine and nitrogen source for facile access to a series of
fluorinated azaꢀheterocycles 3,3ꢀdifluoroꢀ1Hꢀpyrrolꢀ2(3H)ꢀones11 (Scheme 1).
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We began our investigation utilizing the reaction between ethynylbenzene 1a and
2ꢀbromoꢀ2,2ꢀdifluoroꢀNꢀ(pꢀtolyl)acetamide 2a as the model reaction (Table 1). With CuI as
the catalyst in the presence of K2CO3 in MeCN, the model reaction was performed at 110 °C
for 2 hour under air, and no desired aminodifluoroalkylation product was observed (Table 1,
entry 1). When 10 mol % pyridine was added to the above reaction, intermolecular
aminodifluoroalkylation product 3a was obtained in 18% (Table 1, entry 2). We were pleased
to discover that 1,10ꢀphenanthroline (Phen) was an extremely efficient ligand for promoting
the reaction, affording 3a in 92% yield (Table 1, entries 3ꢀ5). Control reactions demonstrated
that base and catalyst were essential to the reaction (Table 1, entries 6 and 7). Other bases,
such as KOtBu and Et3N, were not as effective as K2CO3 (Table 1, entries 8 and 9). Further
investigation on different copper salts revealed that CuBr and CuCl was also efficient catalyst
for this transformation, affording product 3a in a satisfying 86% and 90% yield (Table 1,
entries 10 and 11). With Cu(OTf)2 and Cu(OAc)2 as catalysts, 3a was provided in 41% and
45% yields, respectively (Table 1, entries 12 and 13). Other solvents (e.g., EtOH, DMF,
EtOAc) have been examined but did not lead any significant improvement (Table 1, entries
o
14ꢀ16). When the reaction was performed at 90 C, 3a was isolated in 24% yield (Table 1,
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entry 17). It should be noted that the transformation from 1a into 3a represents the first direct
aminodifluoroalkylation from alkynes.
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Table 1 Optimization of the Reaction Conditionsa
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Entry
Metal
Ligand
Additive Solvent
Yield
(%)b
0
1
2
CuI
CuI
none
Pyridine
bipy
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
none
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
EtOH
18
9
3
CuI
4
CuI
Ph3P
7
5
CuI
Phen
Phen
Phen
Phen
Phen
Phen
Phen
Phen
Phen
Phen
Phen
Phen
Phen
92
trace
trace
15
29
86
90
41
45
6
6
CuI
7
none
CuI
K2CO3
KOtBu
Et3N
8
9
CuI
10
11
12
13
14
15
16
17c
CuBr
CuCl
Cu(OTf)2
Cu(OAc)2
CuI
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
CuI
DMF
8
CuI
EtOAc
19
CuI
CH3CN
24
aReactions were carried out with 1a (0.45 mmol), 2a (0.3 mmol), metal (10 mol %), ligand (10 mol %) and additive (2.0
o
b
c
equiv) in 3 mL solvent under air atmosphere at 110 C for 2 h, unless noted otherwise. Yield of the isolated product. The
o
reaction was performed at 90 C. Phen = 1,10ꢀphenanthroline, Tf = trifluoromethanesulfonyl, bipy=2,2'ꢀbipyridine.
With the optimized reaction conditions in hand (Table 1, entry 5), the scope of the
aminodifluoroalkylation of alkynes was examined and the results are shown in Table 2. The
reaction of 2a and variety of alkynes derivatives afforded the desired aminodifluoroalkylation
products 3 in 55ꢀ92%yields. Haloꢀsubstituted phenylacetylenes (1b–1d, 1k, 1l, 1s, 1t) were
tolerated in the aminodifluoroalkylation reaction, and could be very useful for further
transformations. Phenylacetylene substrates bearing electronꢀwithdrawing substituents, such
as F, Cl, Br, and nitro, were effectively converted into the corresponding products in moderate
to excellent yields. Substrates with electronꢀdonating substituents on the aromatic ring
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underwent aminodifluoroalkylation smoothly to afford the desired products (3eꢀ3j, 3nꢀ3r) in
good yields. In addition, heteroaromatic alkyne such as 3ꢀethynylthiophene 1u was also
effective to provide 3u in 72% yield. Internal alkynes were subsequently examined. Starting
from propꢀ1ꢀynꢀ1ꢀylbenzene 1v and butꢀ1ꢀynꢀ1ꢀylbenzene 1w, 3v and 3w could be obtained in
85% and 82%yields, respectively. However, from the substrates hexꢀ1ꢀyne 1x and
diphenylacetylene 1y, no reactions occurred and the substrate 2a was completely recovered.
Remarkably, in all cases, the reactions proceeded smoothly under air and high
regioselectivities were observed.
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Table 2 Reactions of Alkynes 1 with 2aa,b
aReactions were carried out with 1 (0.45 mmol), 2a (0.3 mmol), CuI (10 mol %), Phen (10 mol %) and K2CO3 (2.0 equiv)
o
c
in CH3CN (3 mL) under air atmosphere at 110 C for 2 h. bYield of the isolated product. The reaction was run for 4 h.
To further explore the potential of this efficient aminodifluoroalkylation reaction, a variety
of
αꢀbromodifluoroacetamides were investigated.
As
shown
in Table 3,
αꢀbromodifluoroacetamides with different substituents at the aromatic ring could be converted
to the desired products 4bꢀ4k in moderate to good yields. Slightly decreased but acceptable
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yields were also achieved for reactions starting from orthoꢀsubstituted aryl amides (2i, 2j).
Remarkably, we found that not only Nꢀaryl substrates, but also Nꢀalkyl substrates worked well,
affording 4l and 4m in 68% and 63% yields. However, the desired annulation product was not
observed between the reaction of ethynylbenzene with monofluoroacetamide
2ꢀbromoꢀ2ꢀfluoroꢀNꢀ(pꢀtolyl)acetamide 2n.12
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Table 3 Reactions of Ethynylbenzene 1a with αꢀBromodifluoroacetamides 2a,b
aReactions were carried out with 1a (0.45 mmol),
2
(0.3 mmol), CuI (10 mol %), Phen (10 mol %) and K2CO3
o
(2.0 equiv) in CH3CN (3 mL) under air atmosphere at 110 C for 2 h. bYield of the isolated product.
To gain insight into the mechanism of this transformation, a radical trapping experiment
was performed. When the radical scavenger 2,2,6,6ꢀtetramethylpiperidine Nꢀoxide (TEMPO,
2.0 equiv.) was added to the aminodifluoroalkylation reaction of 1a under the optimal
conditions, no desired products was isolated and 80% 2a was recovered (eq 1). The results
indicate that a radical pathway may be involved under the catalytic system. Based on the
present experimental results and literature precedent, a possible mechanism was proposed as
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described in Scheme 2. Initially, The reaction of CuI and 2b gave a radical intermediate A and
CuII species via a single electron transfer (SET) process.5c Subsequently, addition of the in
situ generated fluoroalkyl radical A to the C−C triple bond of alkyne leads to the formation of
vinyl radical,10c,e which with CuII species to give the intermediate B in the presence of K2CO3.
Nitrogen atom transfer from CuII to the adduct radical produces the aminodifluoroalkylation
product and regenerates CuI,13 which enters into the next catalytic circle. On the other hand,
we could not exclude another pathway: CuIIꢀamido species reacts with vinyl radicals to form
vinylꢀCuIIIꢀamido species C, which then undergoes the final reductive elimination to give the
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desired annulation product. 7a, 10c,e, 14
Scheme 2 Plausible Reaction Mechanism
In summary, we have developed the first example of copperꢀcatalyzed radical
aminodifluoroalkylation
reaction
of
alkynes
for
the
synthesis
of
3,3ꢀdifluoroꢀ1Hꢀpyrrolꢀ2(3H)ꢀones. The high regioselectivity, broad substrate scope, no extra
oxidant, and low loading of the copper catalyst make the aminodifluoroalkylation reactions
very attractive. We believe that it should prompt further research in the area of
transitionꢀmetal catalyzed aminodifluoroalkylation reactions and related chemistry using
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αꢀbromodifluoroacetamides as both difluoroalkyl source and nitrogen source.
EXPERIMENTAL SECTION
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All reagents were purchased from commercial sources and used without further treatment, unless
otherwise indicated. All reactions were run under air with no precautions taken to exclude
moisture. 1H NMR, 13C NMR and 19F NMR spectra were recorded at 25 ºC on a Varian (400 MHz,
100 MHz and 376 MHz). Melting points were obtained with a micro melting point XT4A Beijing
Keyi electrooptic apparatus and are uncorrected. High resolution mass spectra were recorded on
Bruck microtof. All reactions were monitored by TLC with Taizhou GF254 silica gel coated
plates. Flash column chromatography was carried out using 200ꢀ300 mesh silica gel at increased
pressure.
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General procedure for the preparation of 1oꢀ1r. Substrates 1oꢀ1q were prepared by the
reaction of corresponding anilines (1 mmol) and acyl chlorides (1.1 mmol) in CH2Cl2 at room
temperature. Substrates 1r was prepared according to literature procedure.15
General procedure for the preparation of 2 (2a as an example). In a nitrgeonꢀfilled
glovebox, pꢀtoluidine (535.8 mg, 5.0 mmol), ethyl bromodifluoroacetate (785.1 ꢁL, 6.0 mmol),
and La(OTf)3 (146.5 mg, 0.25 mmol) were combined in screwꢀcap test tube. The reaction mixture
o
was stirred at 50 C and monitored by TLC. After the amine was exhausted, the mixture was
purified by silica gel column chromatography to give the corresponding products 2a (1.21 g,
92%).
General procedure for the preparation of 3 and 4 (3a as Example). To a solution of the
2ꢀbromoꢀ2,2ꢀdifluoroꢀNꢀ(pꢀtolyl)acetamide 2a (79.2 mg, 0.3 mmol) in CH3CN (3.0 ml) was added
the ethynylbenzene 1a (49 ꢁL, 0.45 mmol), Phen (5.4 mg, 0.03 mmol), CuI (5.7 mg, 0.03 mmol),
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and K2CO3 (82.9 mg, 0. 6 mmol) in screwꢀcap test tube. The reaction mixture was stirred at 110
oC for 2.0 h. After the reaction finished, the reaction mixture was cooled to room temperature and
quenched by water. The mixture was extracted with EtOAc (5.0 mL×3), the combined organic
phases were dried over anhydrous Na2SO4 and the solvent was evaporated under vacuum. The
residue was purified by column chromatography to give the corresponding products 3a (78.7 mg,
92%).
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Nꢀ(3ꢀethynylphenyl)acetamide 1o
White solid (149.5 mg, 94%). petroleum ether/ethyl acetate = 40:1 as eluent for the column
1
chromatography. mp: 86ꢀ88 ºC. H NMR (400 MHz, CDCl3): δ = 2.13 (s, 3H), 3.04 (s, 1H), 7.20 (d, J
= 6.8 Hz, 2H), 7.48ꢀ7.49 (m, 1H), 7.67 (s, 1H), 8.60 (s, 1H); 13C NMR (100 MHz, CDCl3): δ = 24.2,
77.4, 83.1, 120.7, 122.5, 123.6, 127.8, 128.8, 138.0, 169.4. HRMS (ESIꢀTOF). Calcd for C10H10NO,
[M+H]+ m/z 160.0762, Found 160.0764.
Nꢀ(3ꢀethynylphenyl)pivalamide 1p
White solid (189.0 mg, 94%). petroleum ether/ethyl acetate = 40:1 as eluent for the column
1
chromatography. mp: 144ꢀ146 ºC. H NMR (400 MHz, CDCl3): δ = 1.27 (s, 9H), 3.03 (s, 1H),
7.17ꢀ7.20 (m, 2H), 7.50ꢀ7.53 (m, 1H), 7.56 (s, 1H), 7.64 (s, 1H); 13C NMR (100 MHz, CDCl3): δ =
27.4, 39.5, 77.3, 83.1, 120.8, 122.5, 123.7, 127.7, 128.7, 138.0, 176.8. HRMS (ESIꢀTOF). Calcd for
C13H16NO, [M+H]+ m/z 202.1232, Found 202.1230.
Nꢀ(3ꢀethynylphenyl)benzamide 1q
White solid (198.9 mg, 90%). petroleum ether/ethyl acetate = 40:1 as eluent for the column
1
chromatography. mp: 122ꢀ124 ºC. H NMR (400 MHz, CDCl3): δ = 3.08 (s, 1H), 7.26ꢀ7.31 (m, 2H),
7.44 (t, J = 7.2 Hz, 2H), 7.53 (t, J = 7.2 Hz, 1H), 7.68 (d, J = 7.2 Hz, 1H), 7.77 (s, 1H), 7.84 (d, J = 7.6
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Hz, 2H), 8.12 (s, 1H); 13C NMR (100 MHz, CDCl3): δ = 77.5, 83.1, 120.9, 122.8, 123.8, 127.0, 128.2,
128.7, 129.0, 131.9, 134.6, 138.0, 166.0. HRMS (ESIꢀTOF). Calcd for C15H12NO, [M+H]+ m/z
222.0919, Found 222.0926.
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tertꢀbutyl (3ꢀethynylphenyl)carbamate 1r
White solid (173.7 mg, 80%). petroleum ether/ethyl acetate = 40:1 as eluent for the column
1
chromatography. mp: 70ꢀ72 ºC. H NMR (400 MHz, CDCl3): δ = 1.50 (s, 9H), 3.04 (s, 1H), 6.75 (s,
1H), 7.13 (d, J = 7.6 Hz, 1H), 7.20 (t, J = 7.6 Hz, 1H), 7.34 (d, J = 7.6 Hz, 1H), 7.53 (s, 1H); 13C NMR
(100 MHz, CDCl3): δ = 28.2, 77.1, 80.6, 83.3, 119.0, 121.9, 122.6, 126.6, 128.8, 138.4, 152.6. HRMS
(ESIꢀTOF). Calcd for C13H16NO2, [M+H]+ m/z 218.1181, Found 218.1171.
2ꢀbromoꢀ2,2ꢀdifluoroꢀNꢀ(pꢀtolyl)acetamide 2a
White solid (1.21 g, 92%). petroleum ether/ethyl acetate = 90:1 as eluent for the column
1
chromatography. mp: 118ꢀ120 ºC. H NMR (400 MHz, CDCl3): δ = 2.35 (s, 3H), 7.18 (d, J = 8.4 Hz,
2H), 7.45 (d, J = 8.4 Hz, 2H), 7.97 (s, 1H); 13C NMR (100 MHz, CDCl3): δ = 20.9, 111.6 (t, J = 315.0
Hz), 120.5, 129.8, 132.7, 136.1, 157.4 (t, J = 28.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ60.4. HRMS
(ESIꢀTOF) Calcd for C9H9BrF2NO, [M+H]+ m/z 263.9836, Found 263.9828.
2ꢀbromoꢀ2,2ꢀdifluoroꢀNꢀphenylacetamide 2b
White solid (1.12 g, 90%). petroleum ether/ethyl acetate = 90:1 as eluent for the column
1
chromatography. mp: 46ꢀ48 ºC. H NMR (400 MHz, CDCl3): δ = 7.23 (d, J = 7.6 Hz, 1H), 7.40 (t, J =
8.0 Hz, 2H), 7.57 (d, J = 8.0 Hz, 2H), 7.86 (s, 1H); 13C NMR (100 MHz, CDCl3): δ = 111.4 (t, J =
315.0 Hz), 120.6, 126.2, 129.3, 135.2, 157.6 (t, J = 28.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ60.6.
HRMS (ESIꢀTOF) Calcd for C8H7BrF2NO, [M+H]+ m/z 249.9679, Found 249.9680.
2ꢀbromoꢀNꢀ(4ꢀchlorophenyl)ꢀ2,2ꢀdifluoroacetamide 2c
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White solid (1.16 g, 82%). petroleum ether/ethyl acetate = 90:1 as eluent for the column
chromatography. mp: 136ꢀ138 ºC. 1H NMR (400 MHz, CDCl3): δ = 7.37 (d, J = 8.8 Hz, 2H), 7.53 (d, J
= 8.8 Hz, 2H), 7.88 (s, 1H); 13C NMR (100 MHz, CDCl3): δ = 111.3 (t, J = 315.0 Hz), 121.7, 129.5,
131.6, 133.8, 157.5 (t, J = 28.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ60.7. HRMS (ESIꢀTOF) Calcd
for C8H6BrClF2NO, [M+H]+ m/z 283.9289, Found 283.9287.
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2ꢀbromoꢀNꢀ(4ꢀbromophenyl)ꢀ2,2ꢀdifluoroacetamide 2d
White solid (1.36 g, 83%). petroleum ether/ethyl acetate = 90:1 as eluent for the column
chromatography. mp: 144ꢀ146 ºC. 1H NMR (400 MHz, CDCl3): δ = 7.47 (d, J = 8.8 Hz, 2H), 7.52 (d, J
= 8.8 Hz, 2H), 7.87 (s, 1H); 13C NMR (100 MHz, CDCl3): δ = 111.3 (t, J = 315.0 Hz), 119.2, 122.0,
132.4, 134.3, 157.4 (t, J = 28.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ60.7. HRMS (ESIꢀTOF) Calcd
for C8H6Br2F2NO, [M+H]+ m/z 329.8764, Found 329.8770.
2ꢀbromoꢀNꢀ(4ꢀethylphenyl)ꢀ2,2ꢀdifluoroacetamide 2e
White solid (1.26 g, 91%). petroleum ether/ethyl acetate = 90:1 as eluent for the column
1
chromatography. mp: 98ꢀ99 ºC. H NMR (400 MHz, CDCl3): δ = 1.24 (t, J = 7.6 Hz, 3H), 2.65 (q, J =
7.6 Hz, 2H), 7.22 (d, J = 8.4 Hz, 2H), 7.47 (d, J = 8.4 Hz, 2H), 7.84 (s, 1H); 13C NMR (100 MHz,
CDCl3): δ = 15.5, 28.3, 111.6 (t, J = 315.0 Hz), 120.5, 128.7, 132.9, 142.4, 157.4 (t, J = 28.0 Hz); 19F
NMR (376 MHz, CDCl3): δ = ꢀ60.4. HRMS (ESIꢀTOF). Calcd for C10H11BrF2NO, [M+H]+ m/z
277.9992, Found 277.9999.
2ꢀbromoꢀNꢀ(4ꢀ(tertꢀbutyl)phenyl)ꢀ2,2ꢀdifluoroacetamide 2f
White solid (1.37 g, 90%). petroleum ether/ethyl acetate = 90:1 as eluent for the column
1
chromatography. mp: 115ꢀ117 ºC. H NMR (400 MHz, CDCl3): δ = 1.32 (s, 9H), 7.41 (d, J = 8.4 Hz,
2H), 7.49 (d, J = 8.8 Hz, 2H), 7.81 (s, 1H); 13C NMR (100 MHz, CDCl3): δ = 31.2, 34.5, 111.5 (t, J =
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315.0 Hz), 120.3, 126.1, 132.6, 149.4, 157.6 (t, J = 27.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ60.4.
HRMS (ESIꢀTOF). Calcd for C12H15BrF2NO, [M+H]+ m/z 306.0305, Found 306.0309.
2ꢀbromoꢀ2,2ꢀdifluoroꢀNꢀ(4ꢀmethoxyphenyl)acetamide 2g
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White solid (1.31 g, 94%). petroleum ether/ethyl acetate = 90:1 as eluent for the column
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chromatography. mp: 117ꢀ119 ºC. H NMR (400 MHz, CDCl3): δ = 3.81 (s, 3H), 6.91 (d, J = 8.8 Hz,
2H), 7.47 (d, J = 8.8 Hz, 2H), 7.84 (s, 1H); 13C NMR (100 MHz, CDCl3): δ = 55.5, 111.7 (t, J = 315.0
Hz), 114.5, 122.2, 128.1, 157.4 (t, J = 28.0 Hz), 157.7; 19F NMR (376 MHz, CDCl3): δ = ꢀ60.4. HRMS
(ESIꢀTOF) Calcd for C9H9BrF2NO2, [M+H]+ m/z 279.9785, Found 279.9782.
2ꢀbromoꢀ2,2ꢀdifluoroꢀNꢀ(mꢀtolyl)acetamide 2h
White solid (1.18 g, 90%). petroleum ether/ethyl acetate = 90:1 as eluent for the column
chromatography. mp: 60ꢀ61 ºC. 1H NMR (400 MHz, CDCl3): δ = 2.36 (s, 3H), 7.06 (d, J = 7.2 Hz, 1H),
7.27 (t, J = 8.0 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.43 (s, 1H), 8.14 (s, 1H); 13C NMR (100 MHz,
CDCl3): δ = 21.3, 111.5 (t, J = 315.0 Hz), 117.7, 121.2, 127.0, 129.0, 135.1, 139.3, 157.6 (t, J = 28.0
Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ60.5. HRMS (ESIꢀTOF) Calcd for C9H9BrF2NO, [M+H]+ m/z
263.9836, Found 263.9833.
2ꢀbromoꢀ2,2ꢀdifluoroꢀNꢀ(oꢀtolyl)acetamide 2i
White solid (1.12 g, 85%). petroleum ether/ethyl acetate = 90:1 as eluent for the column
chromatography. mp: 72ꢀ74 ºC. 1H NMR (400 MHz, CDCl3): δ = 2.35 (s, 3H), 7.06 (d, J = 7.6 Hz, 1H),
7.27 (t, J = 7.6 Hz, 1H), 7.41 (t, J = 7.6 Hz, 2H), 8.29 (s, 1H); 13C NMR (100 MHz, CDCl3): δ = 21.2,
111.5 (t, J = 315.0 Hz), 117.8, 121.3, 127.0, 129.0, 135.1, 139.2, 157.7 (t, J = 28.0 Hz); 19F NMR (376
MHz, CDCl3): δ = ꢀ60.4. HRMS (ESIꢀTOF). Calcd for C9H9BrF2NO, [M+H]+ m/z 263.9836, Found
263.9830.
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2ꢀbromoꢀ2,2ꢀdifluoroꢀNꢀ(2ꢀmethoxyphenyl)acetamide 2j
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White solid (1.26 g, 90%). petroleum ether/ethyl acetate = 90:1 as eluent for the column
chromatography. mp: 78ꢀ79 ºC. 1H NMR (400 MHz, CDCl3): δ = 3.93 (s, 3H), 6.93 (d, J = 8.0 Hz, 1H),
7.01 (t, J = 8.0 Hz, 1H), 7.16 (t, J = 8.0 Hz, 1H), 8.31 (d, J = 8.0 Hz, 1H), 8.54 (s, 1H); 13C NMR (100
MHz, CDCl3): δ = 55.9, 110.2, 111.6 (t, J = 315.0 Hz), 120.0, 121.2, 125.2, 125.8, 148.4, 157.0 (t, J =
27.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ60.2. HRMS (ESIꢀTOF). Calcd for C9H9BrF2NO2,
[M+H]+ m/z 279.9785, Found 279.9778.
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2ꢀbromoꢀNꢀ(3,4ꢀdimethoxyphenyl)ꢀ2,2ꢀdifluoroacetamide 2k
White solid (1.45 g, 94%). petroleum ether/ethyl acetate = 90:1 as eluent for the column
chromatography. mp: 138ꢀ140 ºC. 1H NMR (400 MHz, CDCl3): δ = 3.89 (s, 3H), 3.91 (s, 3H), 6.86 (d,
J = 8.8 Hz, 1H), 6.98 (dd, J1 = 2.4 Hz, J2 = 8.8 Hz, 1H), 7.32 (d, J = 2.4 Hz, 1H), 7.72 (s, 1H); 13C
NMR (100 MHz, CDCl3): δ = 55.9, 56.0, 105.0, 111.3, 111.6 (t, J = 315.0 Hz), 112.8, 128.7, 147.2,
149.2, 157.4 (t, J = 28.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ60.3. HRMS (ESIꢀTOF). Calcd for
C10H11BrF2NO3, [M+H]+ m/z 309.9890, Found 309.9881.
Nꢀbenzylꢀ2ꢀbromoꢀ2,2ꢀdifluoroacetamide 2l
White solid (1.25 g, 95%). petroleum ether/ethyl acetate = 100:1 as eluent for the column
chromatography. mp: 44ꢀ45 ºC. 1H NMR (400 MHz, CDCl3): δ = 4.49 (d, J = 6.0 Hz, 2H), 6.98 (s, 1H),
7.28ꢀ7.31 (m, 2H), 7.33ꢀ7.39 (m, 3H); 13C NMR (100 MHz, CDCl3): δ = 43.9, 111.7 (t, J = 314.0 Hz),
127.7, 128.0, 128.9, 136.1, 160.0 (t, J = 27.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ60.5. HRMS
(ESIꢀTOF). Calcd for C9H9BrF2NO, [M+H]+ m/z 263.9836, Found 263.9831.
2ꢀbromoꢀ2,2ꢀdifluoroꢀNꢀphenethylacetamide 2m
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White solid (1.32 g, 95%). petroleum ether/ethyl acetate = 100:1 as eluent for the column
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chromatography. mp: 92ꢀ94 ºC. H NMR (400 MHz, CDCl3): δ = 2.91 (t, J = 6.8 Hz, 2H), 3.62 (q, J =
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6.8 Hz, 2H), 6.50 (s, 1H), 7.22 (d, J = 6.8 Hz, 2H), 7.26ꢀ7.29 (m, 1H), 7.35 (t, J = 6.8 Hz, 2H); 13C
NMR (100 MHz, CDCl3): δ = 34.9, 41.3, 111.7 (t, J = 314.0 Hz), 126.9, 128.7, 128.8, 137.7, 160.0 (t, J
= 27.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ60.4. HRMS (ESIꢀTOF). Calcd for C10H11BrF2NO,
[M+H]+ m/z 277.9992, Found 277.9983.
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3,3ꢀdifluoroꢀ5ꢀphenylꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 3a
White solid (78.7 mg, 92%). petroleum ether/ethyl acetate = 50:1 as eluent for the column
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chromatography. mp: 106ꢀ108 ºC. H NMR (400 MHz, CDCl3): δ = 2.32 (s, 3H), 5.63 (t, J = 1.2 Hz,
1H), 6.91 (d, J = 8.4 Hz, 2H), 7.11 (d, J = 8.0 Hz, 2H), 7.18 (d, J = 7.6 Hz, 2H), 7.29 (t, J = 7.6 Hz,
2H), 7.38 (t, J = 7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 21.1, 99.8 (t, J = 23.0 Hz), 112.9 (t, J =
244.0 Hz), 126.5, 127.9, 128.5, 128.8, 129.6, 130.6, 130.9, 137.9, 154.6 (t, J = 11.0 Hz), 166.9 (t, J =
30.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ110.1. HRMS (ESIꢀTOF). Calcd for C17H14F2NO, [M+H]+
m/z 286.1043, Found 286.1042.
3,3ꢀdifluoroꢀ5ꢀ(4ꢀfluorophenyl)ꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 3b
Colorless oil (82.7 mg, 91%). petroleum ether/ethyl acetate = 70:1 as eluent for the column
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chromatography. H NMR (400 MHz, CDCl3): δ = 2.33 (s, 3H), 5.61 (d, J = 1.6 Hz, 1H), 6.90 (d, J =
8.4 Hz, 2H), 6.98 (t, J = 8.4 Hz, 2H), 7.13 (d, J = 8.0 Hz, 2H), 7.16ꢀ7.20 (m, 2H); 13C NMR (100 MHz,
CDCl3): δ = 21.1, 99.7 (t, J = 23.0 Hz), 112.8 (t, J = 244.0 Hz), 115.8 (d, J = 22.0 Hz), 124.9 (d, J = 3.0
Hz), 126.6, 129.8, 130.1 (d, J = 8.0 Hz), 130.8, 138.1, 153.5 (t, J = 11.0 Hz), 163.8 (d, J = 251.0 Hz),
166.7 (t, J = 30.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ110.0, ꢀ108.3. HRMS (ESIꢀTOF). Calcd for
C17H13F3NO, [M+H]+ m/z 304,0949, Found 304,0944.
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5ꢀ(4ꢀchlorophenyl)ꢀ3,3ꢀdifluoroꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 3c
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Colorless oil (81.3 mg, 85%). petroleum ether/ethyl acetate = 70:1 as eluent for the column
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chromatography. H NMR (400 MHz, CDCl3): δ = 2.33 (s, 3H), 5.64 (s, 1H), 6.90 (d, J = 8.0 Hz, 2H),
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7.11ꢀ7.14 (m, 4H), 7.27 (d, J = 8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ = 21.1, 100.1 (t, J = 23.0
Hz), 112.7 (t, J = 244.0 Hz), 126.5, 127.2, 128.9, 129.2, 129.8, 130.7, 136.9, 138.2, 153.4 (t, J = 11.0
Hz), 166.7 (t, J = 30.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ110.1. HRMS (ESIꢀTOF). Calcd for
C17H13ClF2NO, [M+H]+ m/z 320.0654, Found 320.0649.
5ꢀ(4ꢀbromophenyl)ꢀ3,3ꢀdifluoroꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 3d
Colorless oil (89.3 mg, 82%). petroleum ether/ethyl acetate = 60:1 as eluent for the column
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chromatography. H NMR (400 MHz, CDCl3): δ = 2.33 (s, 3H), 5.64 (s, 1H), 6.90 (d, J = 8.0 Hz, 2H),
7.05 (d, J = 8.0 Hz, 2H), 7.13 (d, J = 8.0 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H); 13C NMR (100 MHz,
CDCl3): δ = 21.1, 100.1 (t, J = 23.0 Hz), 112.6 (t, J = 244.0 Hz), 125.2, 126.5, 127.7, 129.4, 129.8,
130.7, 131.9, 138.2, 153.5 (t, J = 11.0 Hz), 166.7 (t, J = 30.0 Hz); 19F NMR (376 MHz, CDCl3): δ =
ꢀ110.2. HRMS (ESIꢀTOF). Calcd for C17H13BrF2NO, [M+H]+ m/z 364.0149, Found 364.0156.
3,3ꢀdifluoroꢀ1,5ꢀdiꢀpꢀtolylꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 3e
Colorless oil (73.6 mg, 82%). petroleum ether/ethyl acetate = 70:1 as eluent for the column
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chromatography. H NMR (400 MHz, CDCl3): δ = 2.33 (s, 6H), 5.58 (s, 1H), 6.91ꢀ6.93 (m, 2H),
7.07ꢀ7.13 (m, 6H); 13C NMR (100 MHz, CDCl3): δ = 21.1, 21.4, 99.1 (t, J = 23.0 Hz), 113.0 (t, J =
244.0 Hz), 125.9, 126.6, 127.9, 129.2, 129.6, 131.1, 137.8, 141.0, 154.6 (t, J = 11.0 Hz), 167.0 (t, J =
30.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ109.8. HRMS (ESIꢀTOF). Calcd for C18H16F2NO, [M+H]+
m/z 300.1200, Found 300.1218.
5ꢀ(4ꢀethylphenyl)ꢀ3,3ꢀdifluoroꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 3f
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Colorless oil (76.1 mg, 81%). petroleum ether/ethyl acetate = 70:1 as eluent for the column
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chromatography. H NMR (400 MHz, CDCl3): δ = 1.21 (t, J = 7.6 Hz, 3H), 2.33 (s, 3H), 2.63 (q, J =
8
9
7.6 Hz, 2H), 5.59 (s, 1H), 6.93 (d, J = 8.0 Hz, 2H), 7.08ꢀ7.13 (m, 6H); 13C NMR (100 MHz, CDCl3): δ
= 15.0, 21.1, 28.6, 99.1 (t, J = 23.0 Hz), 113.0 (t, J = 244.0 Hz), 126.1, 126.6, 127.9, 128.0, 129.6,
131.1, 137.8, 147.2, 154.6 (t, J = 11.0 Hz), 167.0 (t, J = 30.0 Hz); 19F NMR (376 MHz, CDCl3): δ =
ꢀ109.7. HRMS (ESIꢀTOF). Calcd for C19H18F2NO, [M+H]+ m/z 314.1356, Found 314.1353.
3,3ꢀdifluoroꢀ5ꢀ(4ꢀpropylphenyl)ꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 3g
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Colorless oil (81.4 mg, 83%). petroleum ether/ethyl acetate = 70:1 as eluent for the column
1
chromatography. H NMR (400 MHz, CDCl3): δ = 0.91 (t, J = 7.2 Hz, 3H), 1.57ꢀ1.63 (m, 2H), 2.33 (s,
3H), 2.56 (t, J = 7.6 Hz, 2H), 5.59 (s, 1H), 6.92 (d, J = 8.0 Hz, 2H), 7.08ꢀ7.12 (m, 6H); 13C NMR (100
MHz, CDCl3): δ = 13.7, 21.1, 24.1, 37.8, 99.1 (t, J = 23.0 Hz), 113.0 (t, J = 244.0 Hz), 126.1, 126.6,
127.9, 128.6, 129.6, 131.1, 137.8, 145.8, 154.6 (t, J = 11.0 Hz), 167.0 (t, J = 30.0 Hz); 19F NMR (376
MHz, CDCl3): δ = ꢀ109.8. HRMS (ESIꢀTOF). Calcd for C20H20F2NO, [M+H]+ m/z 328.1513, Found
328.1506.
5ꢀ(4ꢀbutylphenyl)ꢀ3,3ꢀdifluoroꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 3h
Colorless oil (83.9 mg, 82%). petroleum ether/ethyl acetate = 70:1 as eluent for the column
1
chromatography. H NMR (400 MHz, CDCl3): δ = 0.91 (t, J = 7.6 Hz, 3H), 1.30ꢀ1.37 (m, 2H),
1.52ꢀ1.60 (m, 2H), 2.33 (s, 3H), 2.56 (t, J = 7.6 Hz, 2H), 5.90 (d, J = 1.2 Hz, 1H), 6.92 (d, J = 8.4 Hz,
2H), 7.06ꢀ7.12 (m, 6H); 13C NMR (100 MHz, CDCl3): δ = 13.8, 21.1, 22.3, 33.1, 35.4, 99.1 (t, J = 23.0
Hz), 113.0 (t, J = 244.0 Hz), 126.0, 126.5, 127.8, 128.5, 129.6, 131.1, 137.8, 146.0, 154.6 (t, J = 11.0
Hz), 167.0 (t, J = 30.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ109.8. HRMS (ESIꢀTOF). Calcd for
C21H22F2NO, [M+H]+ m/z 342.1669, Found 342.1677.
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Yellow oil (85.9 mg, 84%). petroleum ether/ethyl acetate = 70:1 as eluent for the column
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chromatography. H NMR (400 MHz, CDCl3): δ = 1.28 (s, 9H), 2.34 (s, 3H), 5.59 (s, 1H), 6.93 (d, J =
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8.4 Hz, 2H), 7.11 (t, J = 8.4 Hz, 4H), 7.29 (d, J = 8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ = 21.1,
31.1, 34.9, 99.2 (t, J = 23.0 Hz), 113.0 (t, J = 244.0 Hz), 125.4, 125.8, 126.6, 127.7, 129.6, 131.2, 137.8,
154.2, 154.5 (t, J = 11.0 Hz), 167.0 (t, J = 30.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ109.8. HRMS
(ESIꢀTOF). Calcd for C21H22F2NO, [M+H]+ m/z 342.1669, Found 342.1664.
3,3ꢀdifluoroꢀ5ꢀ(4ꢀpentylphenyl)ꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 3j
Yellow oil (85.2 mg, 80%). petroleum ether/ethyl acetate = 70:1 as eluent for the column
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chromatography. H NMR (400 MHz, CDCl3): δ = 0.89 (t, J = 6.8 Hz, 3H), 1.28ꢀ1.35 (m, 4H),
1.55ꢀ1.62 (m, 2H), 2.33 (s, 3H), 2.58 (t, J = 7.6 Hz, 2H), 5.60 (s, 1H), 6.93 (d, J = 8.0 Hz, 2H),
7.09ꢀ7.19 (m, 6H); 13C NMR (100 MHz, CDCl3): δ = 13.9, 21.1, 22.4, 30.6, 31.4, 35.7, 99.1 (t, J = 23.0
Hz), 113.0 (t, J = 244.0 Hz), 126.0, 126.5, 127.8, 128.5, 129.6, 131.1, 137.8, 146.0, 154.6 (t, J = 11.0
Hz), 167.0 (t, J = 30.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ109.7. HRMS (ESIꢀTOF). Calcd for
C22H24F2NO, [M+H]+ m/z 356.1826, Found 356.1821.
3,3ꢀdifluoroꢀ5ꢀ(3ꢀfluorophenyl)ꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 3k
White solid (81.8 mg, 90%). petroleum ether/ethyl acetate = 60:1 as eluent for the column
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chromatography. mp: 109ꢀ110 ºC. H NMR (400 MHz, CDCl3): δ = 2.33 (s, 3H), 5.66 (d, J = 1.6 Hz,
1H), 6.89ꢀ6.92 (m, 3H), 6.97 (d, J = 8.0 Hz, 1H), 7.06ꢀ7.10 (m, 1H), 7.13 (d, J = 8.4 Hz, 2H), 7.24ꢀ7.30
(m, 1H); 13C NMR (100 MHz, CDCl3): δ = 21.1, 100.6 (t, J = 23.0 Hz), 112.6 (t, J = 244.0 Hz), 115.1
(d, J = 23.0 Hz), 117.7 (d, J = 21.0 Hz), 123.8 (d, J = 1.0 Hz), 126.4, 129.8, 130.3 (d, J = 9.0 Hz),
130.7, 130.8 (d, J = 8.0 Hz), 138.2, 153.3 (t, J = 11.0 Hz), 162.3 (d, J = 246.0 Hz), 166.6 (t, J = 30.0
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Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ111.3, ꢀ110.4. HRMS (ESIꢀTOF). Calcd for C17H13F3NO,
[M+H]+ m/z 304,0949, Found 304,0939.
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5ꢀ(3ꢀchlorophenyl)ꢀ3,3ꢀdifluoroꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 3l
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Colorless oil (72.7 mg, 76%). petroleum ether/ethyl acetate = 60:1 as eluent for the column
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chromatography. H NMR (400 MHz, CDCl3): δ = 2.32 (s, 3H), 5.65 (s, 1H), 6.91 (d, J = 8.4 Hz, 2H),
6.98 (d, J = 8.0 Hz, 1H), 7.13 (d, J = 8.0 Hz, 2H), 7.20 (t, J = 8.0 Hz, 1H), 7.26 (s, 1H), 7.35 (d, J = 8.0
Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 21.1, 100.7 (t, J = 23.0 Hz), 112.6 (t, J = 245.0 Hz), 126.1,
126.5, 128.0, 129.7, 129.8, 130.5, 130.6, 130.7, 134.7, 138.2, 153.1 (t, J = 11.0 Hz), 166.6 (t, J = 30.0
Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ110.4. HRMS (ESIꢀTOF). Calcd for C17H13ClF2NO, [M+H]+
m/z 320.0654, Found 320.0649.
3,3ꢀdifluoroꢀ5ꢀ(3ꢀnitrophenyl)ꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 3m
Colorless oil (69.3 mg, 70%). petroleum ether/ethyl acetate = 60:1 as eluent for the column
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chromatography. H NMR (400 MHz, CDCl3): δ = 2.32 (s, 3H), 5.78 (t, J = 1.2 Hz, 1H), 6.92 (d, J =
8.0 Hz, 2H), 7.14 (d, J = 8.4 Hz, 2H), 7.45ꢀ7.51 (m, 2H), 8.12 (s, 1H), 8.22ꢀ8.24 (m, 1H); 13C NMR
(100 MHz, CDCl3): δ = 21.1, 101.6 (t, J = 23.0 Hz), 112.3 (t, J = 245.0 Hz), 123.0, 125.2, 126.2, 129.7,
130.1, 130.2, 130.4, 133.5, 138.7, 148.1, 152.1 (t, J = 11.0 Hz), 166.3 (t, J = 30.0 Hz); 19F NMR (376
MHz, CDCl3): δ = ꢀ110.6. HRMS (ESIꢀTOF). Calcd for C17H13F2N2O3, [M+H]+ m/z 331.0894, Found
331.0903.
3,3ꢀdifluoroꢀ5ꢀ(mꢀtolyl)ꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 3n
Colorless oil (64.6 mg, 72%). petroleum ether/ethyl acetate = 60:1 as eluent for the column
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chromatography. H NMR (400 MHz, CDCl3): δ = 2.28 (s, 3H), 2.32 (s, 3H), 5.61 (s, 1H), 6.88ꢀ6.93
(m, 3H), 7.07ꢀ7.19 (m, 5H); 13C NMR (100 MHz, CDCl3): δ = 21.1, 21.3, 99.6 (t, J = 23.0 Hz), 112.9 (t,
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J = 244.0 Hz), 125.1, 126.5, 128.2, 128.5, 128.7, 129.6, 131.0, 131.4, 137.8, 138.4, 154.7 (t, J = 11.0
Hz), 166.9 (t, J = 30.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ110.1. HRMS (ESIꢀTOF). Calcd for
C18H16F2NO, [M+H]+ m/z 300.1200, Found 300.1193.
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Nꢀ(3ꢀ(4,4ꢀdifluoroꢀ5ꢀoxoꢀ1ꢀ(pꢀtolyl)ꢀ4,5ꢀdihydroꢀ1Hꢀpyrrolꢀ2ꢀyl)phenyl)acetamide 3o
White solid (69.8 mg, 68%). petroleum ether/ethyl acetate = 40:1 as eluent for the column
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chromatography. mp: 136ꢀ138 ºC. H NMR (400 MHz, CDCl3): δ = 2.12 (s, 3H), 2.29 (s, 3H), 5.60 (s,
1H), 6.75 (d, J = 7.2 Hz, 1H), 6.89 (d, J = 8.0 Hz, 2H), 7.08 (d, J = 7.6 Hz, 2H), 7.15 (t, J = 8.0 Hz,
1H), 7.49 (d, J = 8.0 Hz, 1H), 7.56 (s, 1H), 7.69 (s, 1H); 13C NMR (100 MHz, CDCl3): δ = 21.0, 24.4,
100.2 (t, J = 23.0 Hz), 112.8 (t, J = 244.0 Hz), 118.9, 121.6, 123.5, 126.4, 129.0, 129.4, 129.7, 130.8,
138.0, 138.5, 154.2 (t, J = 11.0 Hz), 167.0 (t, J = 30.0 Hz), 168.6; 19F NMR (376 MHz, CDCl3): δ =
ꢀ110.2. HRMS (ESIꢀTOF). Calcd for C19H17F2N2O2, [M+H]+ m/z 343.1258, Found 343.1251.
Nꢀ(3ꢀ(4,4ꢀdifluoroꢀ5ꢀoxoꢀ1ꢀ(pꢀtolyl)ꢀ4,5ꢀdihydroꢀ1Hꢀpyrrolꢀ2ꢀyl)phenyl)pivalamide 3p
White solid (78.4 mg, 68%). petroleum ether/ethyl acetate = 40:1 as eluent for the column
chromatography. mp: 178ꢀ179 ºC. 1H NMR (400 MHz, DMSO): δ = 1.21 (s, 9H), 2.27 (s, 3H), 6.07 (s,
1H), 6.70 (d, J = 7.6 Hz, 1H), 7.03 (d, J = 8.0 Hz, 2H), 7.18 (t, J = 8.0 Hz, 3H), 7.67 (d, J = 8.0 Hz,
1H), 7.89 (s, 1H), 9.34 (s, 1H); 13C NMR (100 MHz, DMSO): δ = 25.8, 32.3, 44.4, 104.5 (t, J = 23.0
Hz), 118.5 (t, J = 243.0 Hz), 124.8, 127.2, 127.7, 132.3, 133.6, 133.8, 134.7, 136.0, 142.9, 145.0, 160.0
(t, J = 11.0 Hz), 171.6 (t, J = 30.0 Hz), 181.8; 19F NMR (376 MHz, DMSO): δ = ꢀ108.9. HRMS
(ESIꢀTOF). Calcd for C22H23F2N2O2, [M+H]+ m/z 385.1728, Found 385.1729.
Nꢀ(3ꢀ(4,4ꢀdifluoroꢀ5ꢀoxoꢀ1ꢀ(pꢀtolyl)ꢀ4,5ꢀdihydroꢀ1Hꢀpyrrolꢀ2ꢀyl)phenyl)benzamide 3q
White solid (86.1 mg, 71%). petroleum ether/ethyl acetate = 40:1 as eluent for the column
chromatography. mp: 170ꢀ171 ºC. 1H NMR (400 MHz, DMSO): δ = 2.28 (s, 3H), 6.10 (s, 1H), 6.82 (d,
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J = 7.6 Hz, 1H), 7.06 (d, J = 8.0 Hz, 2H), 7.19 (d, J = 8.0 Hz, 2H), 7.28 (t, J = 8.0 Hz, 1H), 7.55 (t, J =
7.6 Hz, 2H), 7.61 (t, J = 7.2 Hz, 1H), 7.79 (d, J = 8.0 Hz, 1H), 7.94 (d, J = 7.2 Hz, 2H), 8.00 (s, 1H),
10.39 (s, 1H); 13C NMR (100 MHz, DMSO): δ = 21.0, 99.9 (t, J = 23.0 Hz), 113.8 (t, J = 243.0 Hz),
120.1, 122.7, 123.6, 127.5, 128.1, 128.9, 129.2, 129.3, 130.0, 131.3, 132.2, 135.1, 138.1, 140.0, 155.2
(t, J = 11.0 Hz), 166.2, 166.9 (t, J = 30.0 Hz); 19F NMR (376 MHz, DMSO): δ = ꢀ108.8. HRMS
(ESIꢀTOF). Calcd for C24H19F2N2O2, [M+H]+ m/z 405.1415, Found 405.1423.
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tertꢀbutyl (3ꢀ(4,4ꢀdifluoroꢀ5ꢀoxoꢀ1ꢀ(pꢀtolyl)ꢀ4,5ꢀdihydroꢀ1Hꢀpyrrolꢀ2ꢀyl)phenyl)carbamate 3r
White solid (76.8 mg, 64%). petroleum ether/ethyl acetate = 40:1 as eluent for the column
chromatography. mp: 147ꢀ148 ºC. 1H NMR (400 MHz, CDCl3): δ = 1.51 (s, 9H), 2.31 (s, 3H), 5.63 (s,
1H), 6.48 (s, 1H), 6.69 (d, J = 7.6 Hz, 1H), 6.92 (d, J = 8.0 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H), 7.15 (d, J
= 8.0 Hz, 1H), 7.29 (d, J = 8.0 Hz, 1H), 7.45 (s, 1H); 13C NMR (100 MHz, CDCl3): δ = 21.1, 28.3, 81.1,
100.1 (t, J = 23.0 Hz), 112.8 (t, J = 244.0 Hz), 117.6, 120.3, 122.4, 126.5, 129.0, 129.7, 130.9, 137.8,
138.8, 152.4, 154.3 (t, J = 11.0 Hz), 166.9 (t, J = 30.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ110.2.
HRMS (ESIꢀTOF). Calcd for C22H23F2N2O3, [M+H]+ m/z 401.1677, Found 401.1676.
3,3ꢀdifluoroꢀ5ꢀ(2ꢀfluorophenyl)ꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 3s
Colorless oil (53.6 mg, 59%). petroleum ether/ethyl acetate = 60:1 as eluent for the column
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chromatography. H NMR (400 MHz, CDCl3): δ = 2.29 (s, 3H), 5.70 (s, 1H), 6.91 (d, J = 8.0 Hz, 2H),
7.00 (t, J = 9.2 Hz, 1H), 7.07 (d, J = 8.4 Hz, 2H), 7.11 (d, J = 7.6 Hz, 1H), 7.20 (t, J = 6.8 Hz, 1H),
7.35ꢀ7.40 (m, 1H); 13C NMR (100 MHz, CDCl3): δ = 21.1, 102.5 (dt, J1 = 3.0 Hz, J2 = 23.0 Hz), 112.5
(t, J = 245.0 Hz), 116.2 (d, J = 21.0 Hz), 117.3 (d, J = 14.0 Hz), 124.3 (d, J = 3.0 Hz), 126.1, 129.5,
130.2 (d, J = 2.0 Hz), 130.7, 132.6 (d, J = 8.0 Hz), 137.9, 149.7 (t, J = 11.0 Hz), 159.5 (d, J = 251.0
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Hz), 166.1 (t, J = 30.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ111.2, ꢀ110.0. HRMS (ESIꢀTOF). Calcd
for C17H13F3NO, [M+H]+ m/z 304,0949, Found 304,0950.
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Colorless oil (52.6 mg, 55%). petroleum ether/ethyl acetate = 60:1 as eluent for the column
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chromatography. H NMR (400 MHz, CDCl3): δ = 2.26 (s, 3H), 5.64 (d, J = 1.2 Hz, 1H), 6.90 (d, J =
6.8 Hz, 2H), 7.03 (d, J = 7.6 Hz, 2H), 7.24ꢀ7.32 (m, 4H); 13C NMR (100 MHz, CDCl3): δ = 21.0, 102.5
(t, J = 23.0 Hz), 112.6 (t, J = 245.0 Hz), 126.3, 126.9, 128.5, 129.4, 130.0, 130.4, 130.7, 131.6, 133.1,
137.9, 152.4 (t, J = 11.0 Hz), 165.9 (t, J = 30.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ111.7. HRMS
(ESIꢀTOF). Calcd for C17H13ClF2NO, [M+H]+ m/z 320.0654, Found 320.0652.
3,3ꢀdifluoroꢀ5ꢀ(thiophenꢀ3ꢀyl)ꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 3u
White solid (62.9 mg, 72%). petroleum ether/ethyl acetate = 60:1 as eluent for the column
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chromatography. mp: 76ꢀ78 ºC. H NMR (400 MHz, CDCl3): δ = 2.39 (s, 3H), 5.66 (s, 1H), 6.95 (d, J
= 5.2 Hz, 1H), 6.99 (s, 1H), 7.04 (d, J = 8.0 Hz, 2H), 7.21 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 2.4 Hz, 1H);
13C NMR (100 MHz, CDCl3): δ = 21.2, 98.0 (t, J = 23.0 Hz), 113.0 (t, J = 244.0 Hz), 126.4, 126.6,
127.3, 127.5, 129.4, 129.9, 131.1, 138.7, 149.2 (t, J = 11.0 Hz), 166.9 (t, J = 30.0 Hz); 19F NMR (376
MHz, CDCl3): δ = ꢀ109.6. HRMS (ESIꢀTOF). Calcd for C15H12F2NOS, [M+H]+ m/z 292.0608, Found
292.0610.
3,3ꢀdifluoroꢀ5ꢀphenylꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 3v
White solid (76.3 mg, 85%). petroleum ether/ethyl acetate = 60:1 as eluent for the column
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chromatography. mp: 112ꢀ113 ºC. H NMR (400 MHz, CDCl3): δ = 1.91 (t, J = 2.4 Hz, 3H), 2.27 (s,
3H), 6.84 (d, J = 8.4 Hz, 2H), 7.04 (d, J = 8.0 Hz, 2H), 7.11ꢀ7.13 (m, 2H), 7.28ꢀ7.36 (m, 3H); 13C
NMR (100 MHz, CDCl3): δ = 7.1, 21.0, 108.5 (t, J = 22.0 Hz), 113.0 (t, J = 246.0 Hz), 126.4, 128.0,
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128.4, 129.1, 129.5, 129.7, 131.0, 137.4, 146.2 (t, J = 10.0 Hz), 166.3 (t, J = 30.0 Hz); 19F NMR (376
MHz, CDCl3): δ = ꢀ116.8. HRMS (ESIꢀTOF). Calcd for C18H16F2NO, [M+H]+ m/z 300.1200, Found
300.1200.
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3,3ꢀdifluoroꢀ5ꢀphenylꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 3w
Colorless oil (77.0 mg, 82%). petroleum ether/ethyl acetate = 60:1 as eluent for the column
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chromatography. H NMR (400 MHz, CDCl3): δ = 1.20 (t, J = 7.6 Hz, 3H), 2.26 (s, 3H), 2.34 (q, J =
7.6 Hz, 3H), 6.85 (d, J = 8.0 Hz, 2H), 7.03 (d, J = 8.0 Hz, 2H), 7.13 (d, J = 6.4 Hz, 2H), 7.28ꢀ7.36 (m,
3H); 13C NMR (100 MHz, CDCl3): δ = 13.8, 16.4, 21.0, 113.8 (t, J = 246.0 Hz), 113.9 (t, J = 20.0 Hz),
126.4, 128.1, 128.4, 128.9, 129.4, 129.7, 130.9, 137.4, 146.6 (t, J = 10.0 Hz), 166.2 (t, J = 30.0 Hz); 19
F
NMR (376 MHz, CDCl3): δ = ꢀ114.4. HRMS (ESIꢀTOF). Calcd for C19H18F2NO, [M+H]+ m/z
314.1356, Found 314.1356.
3,3ꢀdifluoroꢀ1,5ꢀdiphenylꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 4b
Colorless oil (65.1 mg, 80%). petroleum ether/ethyl acetate = 60:1 as eluent for the column
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chromatography. H NMR (400 MHz, CDCl3): δ = 5.66 (s, 1H), 7.04 (d, J = 6.8 Hz, 2H), 7.18 (d, J =
7.2 Hz, 2H), 7.27ꢀ7.33 (m, 5H), 7.38 (t, J = 7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 100.0 (t, J =
23.0 Hz), 112.8 (t, J = 244.0 Hz), 126.7, 127.8, 127.9, 128.5, 128.7, 129.0, 130.7, 133.5, 154.5 (t, J =
11.0 Hz), 166.7 (t, J = 30.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ109.9. HRMS (ESIꢀTOF). Calcd
for C16H12F2NO, [M+H]+ m/z 272.0887, Found 272.0888.
1ꢀ(4ꢀchlorophenyl)ꢀ3,3ꢀdifluoroꢀ5ꢀphenylꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 4c
Colorless oil (59.5 mg, 65%). petroleum ether/ethyl acetate = 60:1 as eluent for the column
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chromatography. H NMR (400 MHz, CDCl3): δ = 5.66 (s, 1H), 6.96 (d, J = 8.4 Hz, 2H), 7.17 (d, J =
7.6 Hz, 2H), 7.27ꢀ7.34 (m, 4H), 7.41 (d, J = 7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 100.4 (t, J
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= 24.0 Hz), 112.7 (t, J = 244.0 Hz), 127.8, 127.9, 128.4, 128.7, 129.2, 130.9, 132.1, 133.6, 154.0 (t, J =
11.0 Hz), 166.5 (t, J = 30.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ109.7. HRMS (ESIꢀTOF). Calcd
for C16H11ClF2NO, [M+H]+ m/z 306.0497, Found 306.0487.
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1ꢀ(4ꢀbromophenyl)ꢀ3,3ꢀdifluoroꢀ5ꢀphenylꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 4d
Colorless oil (71.0 mg, 68%). petroleum ether/ethyl acetate = 60:1 as eluent for the column
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chromatography. H NMR (400 MHz, CDCl3): δ = 5.66 (s, 1H), 6.90 (d, J = 8.8 Hz, 2H), 7.17 (d, J =
7.6 Hz, 2H), 7.32 (d, J = 7.6 Hz, 2H), 7.40ꢀ7.45 (m, 3H); 13C NMR (100 MHz, CDCl3): δ = 100.5 (t, J
= 24.0 Hz), 112.7 (t, J = 244.0 Hz), 121.6, 127.9, 128.1, 128.4, 128.7, 130.9, 132.2, 132.6, 154.0 (t, J =
11.0 Hz), 166.5 (t, J = 30.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ109.7. HRMS (ESIꢀTOF). Calcd
for C16H11BrF2NO, [M+H]+ m/z 349.9992, Found 349.9987.
1ꢀ(4ꢀethylphenyl)ꢀ3,3ꢀdifluoroꢀ5ꢀphenylꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 4e
Colorless oil (75.3 mg, 84%). petroleum ether/ethyl acetate = 60:1 as eluent for the column
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chromatography. H NMR (400 MHz, CDCl3): δ = 1.21 (t, J = 7.6 Hz, 3H), 2.62 (q, J = 7.6 Hz, 2H),
5.63 (s, 1H), 6.94 (d, J = 8.4 Hz, 2H), 7.14 (d, J = 8.0 Hz, 2H), 7.19 (d, J = 7.6 Hz, 2H), 7.29 (t, J = 7.6
Hz, 2H), 7.38 (t, J = 7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 15.2, 28.4, 99.8 (t, J = 23.0 Hz),
112.9 (t, J = 244.0 Hz), 126.5, 127.9, 128.4, 128.5, 128.8, 130.6, 131.1, 144.1, 154.6 (t, J = 11.0 Hz),
166.9 (t, J = 30.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ110.0. HRMS (ESIꢀTOF). Calcd for
C18H16F2NO, [M+H]+ m/z 300.1200, Found 300.1190.
1ꢀ(4ꢀ(tertꢀbutyl)phenyl)ꢀ3,3ꢀdifluoroꢀ5ꢀphenylꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 4f
White solid (81.4 mg, 83%). petroleum ether/ethyl acetate = 60:1 as eluent for the column
chromatography. mp: 121ꢀ123 ºC. 1H NMR (400 MHz, CDCl3): δ = 1.29 (s, 9H), 5.65 (s, 1H), 6.96 (d,
J = 8.4 Hz, 2H), 7.20 (d, J = 7.6 Hz, 2H), 7.28ꢀ7.34 (m, 4H), 7.39 (t, J = 7.6 Hz, 1H); 13C NMR (100
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MHz, CDCl3): δ = 31.2, 34.6, 99.8 (t, J = 23.0 Hz), 112.9 (t, J = 244.0 Hz), 125.9, 126.1, 127.9, 128.4,
128.8, 130.6, 130.8, 151.0, 154.6 (t, J = 11.0 Hz), 166.9 (t, J = 30.0 Hz); 19F NMR (376 MHz, CDCl3):
δ = ꢀ110.0. HRMS (ESIꢀTOF). Calcd for C20H20F2NO, [M+H]+ m/z 328.1513, Found 328.1518.
3,3ꢀdifluoroꢀ1ꢀ(4ꢀmethoxyphenyl)ꢀ5ꢀphenylꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 4g
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White solid (77.7 mg, 86%). petroleum ether/ethyl acetate = 60:1 as eluent for the column
chromatography. mp: 142ꢀ143 ºC. 1H NMR (400 MHz, CDCl3): δ = 3.78 (s, 3H), 5.62 (s, 1H), 6.82 (d,
J = 8.8 Hz, 2H), 6.96 (d, J = 8.8 Hz, 2H), 7.18 (d, J = 7.6 Hz, 2H), 7.29 (t, J = 7.6 Hz, 2H), 7.38 (t, J =
7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 55.4, 99.6 (t, J = 23.0 Hz), 112.8 (t, J = 244.0 Hz),
114.3, 126.2, 128.0, 128.0, 128.5, 128.7, 130.6, 154.6 (t, J = 11.0 Hz), 159.0, 167.0 (t, J = 30.0 Hz); 19
F
NMR (376 MHz, CDCl3): δ = ꢀ110.2. HRMS (ESIꢀTOF). Calcd for C17H14F2NO2, [M+H]+ m/z
302.0993, Found 302.0984.
3,3ꢀdifluoroꢀ5ꢀphenylꢀ1ꢀ(mꢀtolyl)ꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 4h
Colorless oil (71.9 mg, 84%). petroleum ether/ethyl acetate = 60:1 as eluent for the column
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chromatography. H NMR (400 MHz, CDCl3): δ = 2.30 (s, 3H), 5.65 (s, 1H), 6.77 (d, J = 7.6 Hz, 1H),
6.94 (s, 1H), 7.10 (d, J = 7.2 Hz, 1H), 7.16ꢀ7.21 (m, 3H), 7.30 (t, J = 7.6 Hz, 2H), 7.39 (t, J = 7.2 Hz,
1H); 13C NMR (100 MHz, CDCl3): δ = 21.2, 99.8 (t, J = 23.0 Hz), 112.8 (t, J = 244.0 Hz), 123.7, 127.3,
127.9, 128.4, 128.7, 128.8, 130.6, 133.5, 139.1, 154.6 (t, J = 11.0 Hz), 166.8 (t, J = 30.0 Hz); 19F NMR
(376 MHz, CDCl3): δ = ꢀ110.0. HRMS (ESIꢀTOF). Calcd for C17H14F2NO, [M+H]+ m/z 286.1043,
Found 286.1033.
3,3ꢀdifluoroꢀ5ꢀphenylꢀ1ꢀ(oꢀtolyl)ꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 4i
Colorless oil (62.4 mg, 73%). petroleum ether/ethyl acetate = 60:1 as eluent for the column
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chromatography. H NMR (400 MHz, CDCl3): δ = 2.19 (s, 3H), 5.66 (d, J = 2.0 Hz, 1H), 6.95 (d, J =
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8.0 Hz, 1H), 7.14 (d, J = 7.2 Hz, 3H), 7.23ꢀ7.27 (m, 4H), 7.35 (t, J = 7.6 Hz, 1H); 13C NMR (100 MHz,
CDCl3): δ = 17.9, 99.3 (t, J = 23.0 Hz), 112.8 (t, J = 244.0 Hz), 126.8, 127.6, 128.5, 128.5, 128.8,
129.1, 130.7, 131.3, 132.8, 136.3, 154.9 (t, J = 11.0 Hz), 166.7 (t, J = 30.0 Hz); 19F NMR (376 MHz,
CDCl3): δ = ꢀ110.6. HRMS (ESIꢀTOF). Calcd for C17H14F2NO, [M+H]+ m/z 286.1043, Found
286.1045.
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1ꢀ(3,4ꢀdimethoxyphenyl)ꢀ3,3ꢀdifluoroꢀ5ꢀphenylꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 4j
Colorless oil (75.0 mg, 83%). petroleum ether/ethyl acetate = 60:1 as eluent for the column
1
chromatography. H NMR (400 MHz, CDCl3): δ = 3.52 (s, 3H), 5.59 (s, 1H), 6.80 (d, J = 8.4 Hz, 1H),
6.98 (t, J = 7.6 Hz, 1H), 7.19ꢀ7.35 (m, 7H); 13C NMR (100 MHz, CDCl3): δ = 55.3, 98.5 (t, J = 23.0
Hz), 112.1, 113.0 (t, J = 244.0 Hz), 120.8, 122.5, 127.1, 128.1, 129.5, 129.6, 130.2, 130.2, 154.9, 155.7
(t, J = 11.0 Hz), 167.2 (t, J = 30.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ111.1 (d, J = 304.6 Hz, 1F),
ꢀ109.4 (d, J = 300.8 Hz, 1F). Calcd for C17H14F2NO2, [M+H]+ m/z 302.0993, Found 302.0991.
1ꢀ(3,4ꢀdimethoxyphenyl)ꢀ3,3ꢀdifluoroꢀ5ꢀphenylꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 4k
White solid (88.4 mg, 89%). petroleum ether/ethyl acetate = 60:1 as eluent for the column
chromatography. mp: 130ꢀ131 ºC. 1H NMR (400 MHz, CDCl3): δ = 3.68 (s, 3H), 3.84 (s, 3H), 5.63 (d,
J = 2.0 Hz, 1H), 6.51 (d, J = 2.4 Hz, 1H), 6.61 (dd, J1 = 2.4 Hz, J2 = 8.8 Hz, 1H), 6.77 (d, J = 8.4 Hz,
1H), 7.19 (t, J = 7.2 Hz, 2H), 7.29 (t, J = 7.6 Hz, 2H), 7.38 (t, J = 7.6 Hz, 1H); 13C NMR (100 MHz,
CDCl3): δ = 55.9, 55.9, 99.5 (t, J = 23.0 Hz), 110.4, 110.9, 112.8 (t, J = 244.0 Hz), 119.3, 126.3, 127.9,
128.4, 128.8, 130.5, 148.5, 149.0, 154.6 (t, J = 11.0 Hz), 166.8 (t, J = 30.0 Hz); 19F NMR (376 MHz,
CDCl3): δ = ꢀ110.2. HRMS (ESIꢀTOF). Calcd for C18H16F2NO3, [M+H]+ m/z 332.1098, Found
332.1096.
1ꢀbenzylꢀ3,3ꢀdifluoroꢀ5ꢀphenylꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 4l
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Colorless oil (58.2 mg, 68%). petroleum ether/ethyl acetate = 70:1 as eluent for the column
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chromatography. H NMR (400 MHz, CDCl3): δ = 4.65 (s, 2H), 5.42 (s, 1H), 6.89ꢀ6.92 (m, 2H),
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7.20ꢀ7.23 (m, 5H), 7.38 (t, J = 7.2 Hz, 2H), 7.47 (t, J = 7.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ =
44.4, 100.0 (t, J = 23.0 Hz), 113.0 (t, J = 244.0 Hz), 127.2, 127.7, 127.9, 128.7, 128.7, 129.0, 130.7,
135.8, 155.0 (t, J = 11.0 Hz), 168.1 (t, J = 30.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ112.2. HRMS
(ESIꢀTOF). Calcd for C17H14F2NO, [M+H]+ m/z 286.1043, Found 286.1037.
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3,3ꢀdifluoroꢀ1ꢀphenethylꢀ5ꢀphenylꢀ1Hꢀpyrrolꢀ2(3H)ꢀone 4m
Colorless oil (56.6 mg, 63%). petroleum ether/ethyl acetate = 70:1 as eluent for the column
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chromatography. H NMR (400 MHz, CDCl3): δ = 2.68 (t, J = 7.2 Hz, 2H), 3.70 (t, J = 7.2 Hz, 2H),
5.33 (s, 1H), 6.91ꢀ6.93 (m, 2H), 7.20ꢀ7.26 (m, 5H), 7.43ꢀ7.53 (m, 3H); 13C NMR (100 MHz, CDCl3): δ
= 34.3, 42.3, 99.7 (t, J = 23.0 Hz), 112.8 (t, J = 244.0 Hz), 126.7, 127.7, 128.6, 128.8, 128.9, 129.0,
130.6, 137.3, 154.9 (t, J = 11.0 Hz), 167.9 (t, J = 30.0 Hz); 19F NMR (376 MHz, CDCl3): δ = ꢀ112.8.
HRMS (ESIꢀTOF). Calcd for C18H16F2NO, [M+H]+ m/z 300.1200, Found 300.1204.
ASSOCIATED CONTENT
Supporting Information. 1H NMR, 13C NMR and 19F NMR spectra for compounds 1, 2, 3 and 4.
This material is available free of charge via the Internet at http://pubs. acs.org.
AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: luyh086@nenu.edu.cn.
*Eꢀmail: zhangq651@nenu.edu.cn.
Notes
The authors declare no competing financial interests.
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ACKNOWLEDGMENT
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We gratefully acknowledge the Henan Province Key Laboratory of New OptoꢀElectronic
Functional Materials, the Science & Technology Foundation of Henan Province, the National NSF
of China (21372041) and Jilin Province Key Laboratory of Organic Functional Molecular Design
& Synthesis (130028651) for financial support.
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